Gut microbiota role in irritable bowel syndrome: New therapeutic strategies

Abstract

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.

Keywords: Antibiotics; Fecal transplantation; Gut microbiota; Irritable bowel syndrome; Prebiotics; Probiotics; Synbiotics.

Figure 1

Gut microbiota influences the bidirectional communication between the enteric nervous system and the central nervous system, modulating gut development and several physiological functions, including intestinal motility, sensitivity, secretion and immunity. In irritable bowel syndrome (IBS), the altered composition and/or activity of microbiota may induce a disruption of this communication leading to activation of immune system and production of pro-inflammatory cytokines, production of microbial metabolites as short-chain fatty acids (SCFAs) that are toxic at high concentration, activation of hypothalamic-pituitary-adrenal (HPA) axis with increase of cortisol that feeds back to the pituitary, hypothalamus (HYP), amygdala (AMG), hippocampus (HIPP) and prefrontal cortex to shut off the HPA axis and increase of corticotropin releasing factor (CRF). These effects lead to alterations of intestinal motility and sensation, disruption of epithelial barrier and impaired production of neurotransmitters with an increased response to stressful events. On turn, stress may provoke systemic pro-inflammatory cytokines production that activates the HPA axis that signals to both enteric nervous system and the central nervous system and may alter microbiota composition.